COMMUNICATION
in a lower yield and regioselectivity (Table 1, entry 4). Al-
though an effective reductive coupling reaction also oc-
curred using PEt3, the product was lower in regioselectivity
than that obtained using the PCy3 ligand (Table 1, entry 5).
Triarylphosphine, trialkylphosphite, and diphosphine such as
contrast to aldehydes, ketones such as acetophenone did not
participate in this reaction.
Furthermore, ferrocenecarboxyaldehyde was also shown
to generate 3am as a red solid in high yield with high regio-
and stereoselectivities (Scheme 1). Red single crystals of
PPh3, PACHTUNGTRENNUNG(OMe)3, and dppe did not participate in this reaction
(Table 1, entries 6–8). On the basis of this screen of phos-
phine ligands, the highest yield and complete regio- and ste-
reoselectivities for the formation of reductive coupling prod-
uct 3aa was achieved using the PCy3 ligand in the presence
of BEt3 as the reducing agent.
Next, the nickel-catalyzed regio- and stereoselective re-
ductive coupling reaction using methylenecyclopropane with
retention of the cyclopropane ring was examined using vari-
ous aldehydes as shown in Table 2. The use of electron-do-
nating p-, o-methyl- or p-methoxy-substituted aryl aldehydes
Scheme 1. Ni-catalyzed reductive coupling between 1a and 2m in the
presence of BEt3.
3am suitable for X-ray diffraction were grown from hexane
solution. The ORTEP drawing of 3am is shown in Figure 1,
revealing the stereochemistry of the reductive coupling
product.[15] The methyl group and cyclooctane moiety of the
cyclopropane ring are located cis to each other.
Table 2. Ni-catalyzed reductive coupling between 1 and 2a–l in the pres-
ence of BEt3.[a]
Entry
2
R
Yield
[%][b]
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2 f
2g
2h
2i
Ph
3aa (98)
3ab (90)
3ac (81)[d]
3ad (89)
3ae (95)
3af (86)
3ag (98)
3ah (80)
3ai (95)
3aj (64)
3ak (49)
3al (51)
p-MeC6H4
o-MeC6H4
p-MeOC6H4
p-FC6H4
p-ClC6H4
p-MeO2CC6H4
2-furyl
2-thienyl
3-pyridyl
n-C5H11
Figure 1. ORTEP drawing of 3am with thermal ellipsoids drawn at the
50% probability level.
9
10[c]
11
12
2j
2k
2l
Cy
After demonstrating the scope of substitution patterns of
the aldehydes, we next examined the scope for the methyle-
necyclopropane partner (Table 3). Cycloheptane-fused
methylenecyclopropane 1b provided the corresponding
product 3ba in good yield with complete regio- and stereo-
selectivities (Table 3, entry 1). Although cyclohexane-fused
methylenecyclopropane 1c also participated in this reaction,
the product 3ca was obtained as a mixture with the ring-
opened reductive coupling product (Table 3, entry 2).[16] The
corresponding silylated ring-opened product was obtained in
our report by the reaction between methylenecyclopropane
and aldehyde using nickel-NHC catalyst in the presence of
silane.[6] Cyclooctene-fused methylenecyclopropane 1d also
participated in the reaction and gave the corresponding
product 3da, with retention of the double bond in the cyclo-
octene ring (Table 3, entry 3). The cis-dialkyl chain-substi-
tuted methylenecyclopropane 1e afforded 3ea in high yield
(Table 3, entry 4). Methylenecyclopropanes bearing cis-alkyl
chains with ether functionalities such as silyl ether and
benzyl ether provided the corresponding products 3 fa and
3ga in good yields (Table 3, entries 5 and 6). It should be
[a] [Ni
(cod)2] (0.10 mmol), PCy3 (0.20 mmol), 1a (2.0 mmol),
2
(1.0 mmol), BEt3 (2.0 mmol) and and THF/hexane (3 mL/2 mL) were
employed. [b] Isolated product yield. [c] BEt3 (3.0 mmol). [d] 14% regio-
isomer 3ac-B was also contained.
also afforded product 3 in good to high yields (Table 2, en-
tries 2–4). In the case of sterically hindered o-tolualdehyde
(Table 2, entry 3), reductive coupling products were formed
as a mixture of regioisomers (regioselectivity: 86%). Other
substituted aryl aldehydes bearing electron-withdrawing
groups (fluoro, chloro, and ester) also participated in this re-
action to give the corresponding product 3 (Table 2, en-
tries 5–7). In spite of the use of a Lewis acid (triethylbor-
ane), heteroaryl aldehydes such as 2-furyl, 2-thienyl, and 3-
pyridyl aldehydes reacted to afford the reductive coupling
products 3 selectively (Table 2, entries 8–10).[14] In addition
to the aryl aldehydes, alkyl aldehydes such as 1-hexanal and
cyclohexanecarbaldehyde also participated in this reaction
to afford the corresponding coupling products with complete
regio- and stereoselectivities (Table 2, entries 11 and 12). In
Chem. Eur. J. 2012, 18, 6142 – 6146
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6143